One of the most important challenges of assessing stress in general, and traumatic stress in particular, is the undue reliance on patient self-report and clinical behavioral observations. Components of the salivary proteome are known to manifest the neurobiological response to stressors and their biometric potential could be exploited to transform current research and clinical practice paradigms related to stress-related mental health disorders. The significant problem of traumatic stress disorders provides a compelling translational context for utilizing the differential expression of putative salivary strss biomarkers to facilitate objective characterization of the stress response and provide insights into resilience and vulnerability to stress related psychopathology. By relating temporal changes in domain-knowledge based salivary biomarker patterns to the psychological effects of an extreme stressor, we will verify the discriminate and predictive utility of salivary biomarkers for maladaptive stress reactions such as post-traumatic stress disorder (PTSD) and major depressive episode (MDD). We hypothesize that the expression levels of combinations of putative salivary stress biomarkers, in an at-risk population of trauma patients, will manifest maladaptive stress reactions and predict the development of post-trauma psychopathology. Using prospective-specimen-collection, retrospective-blinded-evaluation (Probe) design criteria in a cohort of 600 patients (training set = 450, validation set= 150) with an index trauma (injury or rape) and through repeat psychological assessments and multiplexed salivary assays, we will (1) Validate the reported associations between individual salivary stress biomarkers and post-trauma psychopathology (PTSD/MDD), (2) Develop a prediction model that combines the individual biomarkers and relates them to post-trauma psychopathology (PTSD/MDD) (3) Determine the performance characteristics of the prediction model of post-trauma psychopathology (PTSD/MDD) and (4) Explore the adjunctive diagnostic utility of salivary stress biomarkers in post-trauma psychopathology (PTSD/MDD). Our overarching goal is to develop point-of-care, salivary biosensors to operationalize the screening, monitoring and risk stratification of traumatized individuals for mental health disorders. The development of salivary biomarker signatures informative of traumatic stress responses through this study is an essential building block for the continued innovation of novel, multiplexed nanosensors that we are developing concomitantly. In the long term, we expect that our interdisciplinary research strategy, incorporating salivary biomarker panels and computational algorithms into behavioral assessments, will create a paradigm shift in the understanding, diagnosis and management of traumatic stress and psychopathology. PUBLIC HEALTH RELEVANCE: Extreme stress affects mental health in many ways. The current reliance on subjective self-reports and clinical behavioral observations often cause emerging mental health problems to be missed until they become established and difficult to treat. We plan to use stress-marker proteins that present in saliva for detecting future mental health problems at an early stage when they are more responsive to treatments.